Human papillomavirus (HPV) is a DNA virus that establishes productive infections in keratinocytes of the skin or mucous membranes. There are over 170 types of HPV, a subset of which HPV types are carcinogenic, including high-risk sexually transmitted types that can develop into genital neoplasias, including cervical intraepithelial neoplasia (CIN), vulvar intraepithelial neoplasia (VIN), penile intraepithelial neoplasia (PIN), and/or anal intraepithelial neoplasia (AIN), for example. HPV—induced cancers arise when viral sequences are integrated into the cellular DNA of host cells. Some of the HPV “early” genes, such as E6 and E7, act as oncogenes that promote tumor growth and malignant transformation.
Ramos et al., (J Immunother 2013; 36:66-76) describes a method for stimulating peripheral blood mononuclear cells to generate T-cells specific for HPV16 E6 and E7. In brief, the method comprises stimulation of peripheral blood mononuclear cells with dendritic cells in which cells are cultured in CTL medium with or without the combination of cytokines IL-6, IL-7, IL-12 and IL-15, a second stimulation in which co-cultures are supplemented with IL-2, and weekly stimulation with pepmix-loaded accessory antigen presenting cells (e.g., B-blasts) in the presence of IL-15. This reference teaches the combination of cytokines IL-6, IL-7, IL-12 and IL-15 is required for expansion of the HPV-specific T-cells from patient samples, for detectable T-cell responses.
The present disclosure provides relief for a long-felt need in the art to treat HPV-associated diseases, including at least for those associated with HPV16 and HPV18, for example.